Neuropathic pain is an intervention-resistant clinical enigma. Relief provided by sympathectomy helps define sympathetic contributions to the maintenance of these pain syndromes. In rat neuropathy models, striking differences seen in the nature, timing and sympathetic dependence of pain behaviors offer a tool for deciphering mechanisms by which nerve injury promotes exaggerated sensory perceptions to stimuli. This project contends that deviations in the site and type of nerve lesion lead to pain behaviors varying in onset, severity, duration, modality and sympathetic dependence. Site and type of nerve injury are critical factors in dictating the completeness and permanence of dermatomal deinnervation and central deafferentation. Nerve growth factor (NGF) is known to produce hyperalgesic responses to evoked stimulation. Deinnervation amplifies peripheral NGF expression which may promote pain behaviors if residual innervation remains or regenerates. Sympathetically dependent pain behaviors are linked to sprouting of sympathetic fibers onto deafferented sensory neurons in the dorsal root ganglion (DRG). NCF is a critical mediator of sympathetic fiber sprouting. Since nerve lesions interfere with axonal NGF transport, injuries that are both more peripheral (less DRG specific) and also regeneration-permissive are likely to provide adequate NGF to avert promiscuous sympathetic rewiring. Rat nerve injury hybrids (site x type) will be performed. Resultant behaviors will characterized and analyzed by lesion variables. lmmunocytochemical labeling of sympathetic markers and NGF will be assessed and correlated at key sites and times. These data will enhance the effort to predict, prevent or intercede in the processes resulting in neuropathic pain in man.